Several regulators of meiosis in S cerevisiae act on the Rim101 pathway, a conserved signal transduction pathway. Homologous pathways promote expression of genes in response to external alkaline pH in other fungi and, as these investigators have recently found, in yeast as well. External pH is a biological signal that governs growth, physiology, and differentiation of virtually all cells, yet there is limited information about the transcriptional responses to external pH changes. The long-term objective of this study is to determine how external pH changes govern responses at the level of gene expression and cellular differentiation. The immediate goal is to define the mechanisms of signal transduction through and output of the Rim101 pathway, and to use this information to develop a framework for understanding the pH response and its relationship to meiosis. Specific aims are to determine the functional relationships among Rim101 pathway members, to determine how the Rim101 pathway governs target gene expression, and to determine the relationship between the Rim101 pathway and functional suppressor genes that can promote alkaline pH responses and meiosis.